A number of gases have been shown to have pharmaceutical action in humans and animals. One such gas is Nitric Oxide (NO) that, when inhaled, acts to dilate blood vessels in the lungs, improving oxygenation of the blood and reducing pulmonary hypertension. In the field of inhalation therapy for various pulmonary conditions such as acute pulmonary vasoconstriction, hypertension and thromboembolism, or inhalation injury, treatment has included the use of the therapeutic gas NO supplied from a gas cylinder. More specifically, this gaseous NO for inhalation therapy is supplied to a patient from a high pressure gas cylinder containing NO. For example, such an approach is disclosed in U.S. Pat. No. 5,558,083 entitled “Nitric Oxide Delivery System”, which is incorporated herein by reference in its entirety.
Unlike supplying NO for inhalation therapy from a high pressure NO cylinder; some have proposed supplying NO for inhalation therapy from a source of Nitrogen Dioxide (NO2), which is toxic, and converting this toxic NO2 into NO using a “cartridge” or “reactor” (NO2-to-NO reactor cartridge) at the patient's bedside. For example, such an approach is disclosed in U.S. Pat. No. 7,560,076 (“the '076 Patent”) issued Jul. 14, 2009 to Rounbehler et al., and assigned to GENO, LLC, which is incorporated herein by reference in its entirety. The NO2-to-NO reactor cartridge in the '076 Patent is filled with a loosely packed powder of a surface-active material (e.g., silica) coated with an aqueous solution of an antioxidant (e.g., aqueous ascorbic acid). Purportedly, the reactor receives NO2 that passes through the loosely packed silica coated with the aqueous ascorbic acid and undergoes a chemical reaction that converts NO2 to NO, which in turn exits the reactor cartridge and is then delivered to the patient.
Substantial patient safety and efficacy concerns arise from converting toxic NO2 to NO at the patient's bedside as proposed because of at least the toxic nature of NO2. For example, as pointed out in the '076 Patent, “unlike NO, the part per million levels of NO2 gas is highly toxic if inhaled and can form nitric and nitrous acid in the lungs.”
Compounding risks relating to such NO2 to NO conversion at the patient's bedside, the ability of these NO2-to-NO reactor cartridges to convert NO2 to NO exhausts as it uses a consumable reactant and this exhaustion results in the breakthrough of toxic NO2, which in turn may be delivered to the patient. Without an indicator (e.g., dosage meter) to the user of the amount of lifetime remaining for the reactor as it exhausts, a user has no way of confirming how much or little lifetime the reactor has prior to at least breakthrough of toxic NO2. This can force the user to guess how much lifetime the reactor has prior to at least breakthrough of toxic NO2; However, factors impacting the lifetime of the reactor and/or breakthrough of toxic NO2 may not be readily attainable by user observation.
Further compounding risks relating to such NO2-to-NO reactor cartridges, the ability of these reactors to convert NO2 to NO (e.g., lifetime) can become compromised resulting in breakthrough of toxic NO2 being delivered to the patient. For example, the reactor can be compromised by a channel that allows NO2 flow through the reactor cartridge without conversion to NO as disclosed in U.S. Pat. No. 8,646,445 (“the '445 Patent”) issued Feb. 11, 2014, to Fine et al., and assigned to GENO, LLC, which is incorporated herein by reference in its entirety. As pointed out in the '445 patent, “Creation of a channel negates the effect of the powder and renders the cartridge useless. This problem is so severe that a packed tube like this can only be used if the cartridge is vertical.”
Another NO2-to-NO reactor cartridge is discussed in U.S. Pat. No. 8,607,785 (“the '785 Patent”) issued Dec. 17, 2013, to Fine et al., and assigned to GENO, LLC, which is incorporated herein by reference in its entirety. Rather than a loosely packed reactor cartridge, the '785 Patent discloses a porous solid structure, which provides a rigid structure coated with an aqueous solution of an antioxidant. However, such a porous solid structure can be brittle and have its structural integrity compromised by sudden shocks or rough handling, as might occur in a clinical setting and/or by user error, handling of the conversion reactor, and environmental factors, to name a few. For example, cracks can be formed in the structure which can provide a channel allowing flow of NO2 through the reactor without conversion to NO, which in turn may be delivered to the patient. Further, cracks in the structure may not be obvious until a gas flow is applied and/or NO2 breakthrough occurs. In another scenario, a crack in the porous solid structure may not initially propagate all the way through the structure until sometime later under routine usage, when a toxic NO2 suddenly exits the reactor cartridge, which in turn may be delivered to the patient. Accordingly, such compromised reactors may have unforeseen shortened lifetimes.
The above are only a few of the exemplary scenarios which can result in a patient receiving toxic NO2 using the proposed techniques of converting toxic NO2 to NO at the patient's bedside using an exhaustible reactor cartridge when lifetime of reactor is unknown to the user. Given the risk of serious injury or death associated with inhalation of NO2 along with compounding factors and/or failure modes which may not be readily attainable by a user (e.g., reactor exhaustion, channeling, compromised reactors, NO2 breakthrough, etc.) a need exists to provide an indicator (e.g., dosage meter) to the user of the amount of lifetime remaining for the reactor.